St John wort and dopamine hydroxylase

[DAVID]

St John wort is a natural anti-depressant; the principal mechanism is NA and 5 HT reuptake and some MAO a inhibition.

But when you read study, you can see that millepertuis inhibe dopamine hydroxylase.

I'm not a expert of brain fonction but I understand that you increase dopamine in the brain but you decrease in the same time brain noradrenaline.

Not so good for people who have noradrenergic depression and fatigue.

[marianco]

Originally Posted by DAVID

St John wort is a natural anti-depressant; the principal mechanism is NA and 5 HT reuptake and some MAO a inhibition.

But when you read study, you can see that millepertuis inhibe dopamine hydroxylase.

I'm not a expert of brain fonction but I understand that you increase dopamine in the brain but you decrease in the same time brain noradrenaline.

Not so good for people who have noradrenergic depression and fatigue.

Actually, St. John's Wort has a very complex group of mechanisms of action, some of which are not yet clear.

Here's an abstract:

Mechanism of action of St John's wort in depression : what is known?
by Butterweck V. CNS Drugs. 2003;17(8):539-62.

Extracts of Hypericum perforatum L. (St John's wort) are now successfully competing for status as a standard antidepressant therapy. Because of this, great effort has been devoted to identifying the active antidepressant compounds in the extract. From a phytochemical point of view, St John's wort is one of the best-investigated medicinal plants. A series of bioactive compounds has been detected in the crude material, namely flavonol derivatives, biflavones, proanthocyanidines, xanthones, phloroglucinols and naphthodianthrones. Although St John's wort has been subjected to extensive scientific studies in the last decade, there are still many open questions about its pharmacology and mechanism of action. Initial biochemical studies reported that St John's wort is only a weak inhibitor of monoamine oxidase-A and -B activity but that it inhibits the synaptosomal uptake of serotonin, dopamine and noradrenaline (norepinephrine) with approximately equal affinity. However, other in vitro binding assays carried out using St John's wort extract demonstrated significant affinity for adenosine, GABA(A), GABA(B) and glutamate receptors. In vivo St John's wort extract leads to a downregulation of beta-adrenergic receptors and an upregulation of serotonin 5-HT(2) receptors in the rat frontal cortex and causes changes in neurotransmitter concentrations in brain areas that are implicated in depression. In studies using the rat forced swimming test, an animal model of depression, St John's wort extracts induced a significant reduction of immobility. In other experimental models of depression, including acute and chronic forms of escape deficit induced by stressors, St John's wort extract was shown to protect rats from the consequences of unavoidable stress. Recent neuroendocrine studies suggest that St John's wort is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function. With regard to the antidepressant effects of St John's wort extract, many of the pharmacological activities appear to be attributable to the naphthodianthrone hypericin, the phloroglucinol derivative hyperforin and several flavonoids. This review integrates new findings of possible mechanisms that may underlie the antidepressant action of St John's wort and its active constituents with a large body of existing literature.

A problem with St. John's Wort is that it stimulates activity of Cytochrome P450 3A4. This potentially can weaken many medications simultaneously taken with St. John's Wort.

Increasing Dopamine while reducing Norepinephrine to treat depression is actually good when it comes to reducing depression.

There is a pathway in the brain by which increased dopamine production can reduce output from the Locus Ceruleus - which produces most of the brain's norepinephrine.

Norepinephrine is a stress signal in the brain produced by the sympathetic nervous system in response to stress. Excessive and prolonged stress can cause adrenal fatigue - which can then result in fatigue, depression, anxiety, and the inability to cope with stress.

One of the reasons stimulants and Bupropion fail to treat depression is that the increase in norepinephrine level they promote can lead to adrenal fatigue and worsening of depressive symptoms. They will only work if the overall dose is not too high, the patient's stresses are low to moderate, and the adrenal glands are fairly healthy.

Increased dopamine is also good in that it stimulates testosterone production. Testosterone can then limit excessive adrenal activity to help prevent adrenal fatigue.

I wonder if a "noradrenergic depression" is actually adrenal fatigue. In adrenal fatigue, sometimes norepinephrine and epinephrine production is reduced.

Increasing norepinephrine is still very useful in reducing chronic pain, when combined with a simultaneous increase in serotonin. Again, this treatment, however, is limited by the health of the adrenal glands.

[pmgamer18]

Some yrs. ago my Dr. tried stimulants to help with my fatigue they drove up my BP and heart rate. So when Concerta came out he tried it I have been on 38mgs for some time now. I am thinking maybe it would be a good Idea to get off this drug. Now that we know I am Hypopituitary and low on cortisol and thyroid. Every time I read that meds like this are hard on adrenals I can't help but think I would be better off not taking this anymore. Yet I don't feel my cortisol levels are low to poor adrenals but the messages not that strong from my pit. Still would it be better to get off Concerta.

[DAVID]

Thank you so much - adrenal fatigue is like " atypical depression". You have adrenal fatigue but a low catecholamine level too. SSRI make some people worse like me

Hydrocortisone and thyroid treament help for people who have a deficit. Sympathic burnout is real. A lack of brain noradrenaline increase fatigue.

I remenber before my treatment of thyroid, I feel so great... you feel that brain are full in energy like a maniac. (high NA Turnover or content)

But when I've beginning thyroid trearment for hypothyroidie, I've never feeling this "brain good feeling" and begin to have lower mood.

I've tring myself tyrosine and moclobemide and coffee for a few year's with good result.
But at this time, this stuff doesn(t work anymore, because I've burning my adrenal).

After 3 year's of hydrocortisone, my adrenal test show again "low adrenal reserve.

Hydrocortisone help fatigue but my mood is low. You need quiet life. I've triing every herbs, high vit C but nothing respond. I TOTALLY AGRY WHEN YOU SAID THAT "again, this treament, however, is limited by the health of the adrenal gland"

In my country, many physicians doesn't known nothing about adrenal fatigue-very difficult to have good advises in this condition. Psychiatre known only SSRI that make you worse.

Anti-aging doctor give you hydrocortisone between 30 at 40 mg of hydrocortisone but doesn't known about brain fonction/neurotransmetteurs/cytokines...

[marianco]

Originally Posted by pmgamer18

Some yrs. ago my Dr. tried stimulants to help with my fatigue they drove up my BP and heart rate. So when Concerta came out he tried it I have been on 38mgs for some time now. I am thinking maybe it would be a good Idea to get off this drug. Now that we know I am Hypopituitary and low on cortisol and thyroid. Every time I read that meds like this are hard on adrenals I can't help but think I would be better off not taking this anymore. Yet I don't feel my cortisol levels are low to poor adrenals but the messages not that strong from my pit. Still would it be better to get off Concerta.

If there is a dopamine deficit or dopamine resistance (where dopamine production is high to compensate for receptors that are only partially sensitive to dopamine), then a person may have a form of attention deficit/hyperactivity disorder for which continuing a stimulant is useful since even testosterone optimization won't increase dopamine levels enough.

If the use of a stimulant is to improve energy level, then it would be far more useful to optimize thyroid function, adrenal function and carbohydrate metabolism (e.g. reducing insulin resistance). After such optimization, the use of a stimulant would be much less necessary, if at all.

[marianco]

Originally Posted by DAVID

Thank you so much - adrenal fatigue is like " atypical depression". You have adrenal fatigue but a low catecholamine level too. SSRI make some people worse like me

Hydrocortisone and thyroid treament help for people who have a deficit. Sympathic burnout is real. A lack of brain noradrenaline increase fatigue.

I remenber before my treatment of thyroid, I feel so great... you feel that brain are full in energy like a maniac. (high NA Turnover or content)

But when I've beginning thyroid trearment for hypothyroidie, I've never feeling this "brain good feeling" and begin to have lower mood.

I've tring myself tyrosine and moclobemide and coffee for a few year's with good result.
But at this time, this stuff doesn(t work anymore, because I've burning my adrenal).

After 3 year's of hydrocortisone, my adrenal test show again "low adrenal reserve.

Hydrocortisone help fatigue but my mood is low. You need quiet life. I've triing every herbs, high vit C but nothing respond. I TOTALLY AGRY WHEN YOU SAID THAT "again, this treament, however, is limited by the health of the adrenal gland"

In my country, many physicians doesn't known nothing about adrenal fatigue-very difficult to have good advises in this condition. Psychiatre known only SSRI that make you worse.

Anti-aging doctor give you hydrocortisone between 30 at 40 mg of hydrocortisone but doesn't known about brain fonction/neurotransmetteurs/cytokines...

Mood has to be separated from energy as conceptual targets of treatment.

Improving energy level involves optimizing thyroid function, adrenal function, and carbohydrate metabolism (e.g. reducing insulin resistance). The end organ targets of the involved hormones must also be in good health. For example, the liver must be in good health so that gluconeogenesis, thyroid hormone activation, etc. can occur.

Mood is a highly complex entity with numerous components. For example, mood is controlled by a multitude of neurotransmitter, hormone, and cytokine activities, as well as the need for adequate nutrient supplies (e.g. vitamins, fats, proteins, minerals, and other substances). Mood is also controlled by psychological factors, other physical health factors, and environmental factors that need to be evaluated and addressed as necessary. A complex coordinated treatment which is customized to a person's condition may be necessary to improve mood.

Certainly the ability to produce norepinephrine is necessary to increase CRH, then ACTH production that increases adrenal cortex hormone production and improves energy level. Norepinephrine also triggers a signal through the peripheral sympathetic nerves that target the adrenal medulla's activity. It is important to understand the pathway by which norepinephrine increases energy level. It is primarily by acting on the adrenal gland. It is thus limited in effectiveness if the adrenal gland is fatigued.

Developmentally the adrenal glands are part of the sympathetic nervous system (the medullary cells primarily though there are also islands of sympathetic nervous system cells within the cortex). The adrenal medulla is a sympathetic nervous system ganglion. Thus one can look at "sympathetic burnout" as adrenal fatigue which also involves the adrenal medulla.

Adrenal fatigue treatments are generally passive - they usually don't directly improve the adrenal glands ability to function. Rather they give the adrenal glands time to rest and recover.

Thyroid hormone optimization is one treatment which can actively improve adrenal function. It does so by increasing the number and size of mitochondria in each of the adrenal gland's cells.

[DAVID]

I understand that everything is important : cytokines, catecholamines , serotonin... hormones, food, environnement. Humans is a very complex machine.

I've reading that antidepressant work after 3 weeks, because you need to wait the post- receptors down regulation.

I remember the first time I've taking effexor 75 mg, I feel so great for one day, but after that the next day I don't have this good effect on mood but paradoxally very bad mood and I have cognitive deficit. CAN YOU EXPLAIN THIS EFFECT !!!!

You are true when you said that there are no happy pill.

[Naturdoc]

From the abstract, I don't see that St J. wort reduces norepineprine. Nor do I believe that increased levels of dopamine will reduce norepineprine. Norepineprine is a metabolic byproduct of Dopamine.
St JohnsWort like many herbs is too complex in its activity. It is doubtful that pharmaceutical research will find the ONE constituent that is causing the response. If there is doubt about neurotransmitter levels-- measure them.